PROTEASE-RESISTANT PRP DEPOSITION IN BRAIN AND NONCENTRAL NERVOUS-SYSTEM TISSUES OF A MURINE MODEL OF BOVINE SPONGIFORM ENCEPHALOPATHY

Infectivity within the central nervous system has been demonstrated by the transmission of bovine spongiform encephalopathy (BSE) from affec ted cattle to inbred laboratory mice, Sedimentable, protease-resistant PrP (PrPSc) has also been extracted from BSE-affected cattle brain. B oth infectivity and PrPSc have been reported in the lymphoreticular ti ssues of sheep and mice clinically and preclinically affected with scr apie. Neither infectivity nor PrPSc has yet been detected in nonneural tissues of naturally occurring, clinical cases of BSE in cattle. We h ave used a murine model of BSE (301V isolate in VM/Dk mice) to investi gate when and where PrPSc accumulates. PrPSc was detected both in brai n and in extraneural sites prior to the onset of clinical symptoms, Th is murine BSE model differs, however, in four important aspects from o ur previously published findings for murine scrapie models: (a) PrPSc was found relatively late into the incubation period; (b) after intrac erebral inoculation, PrPSc was found in brain before it was found in o ther tissues; (c) no PrPSc was found in most of the spleens from clini cally affected animals after intracerebral inoculation; and (d) even a fter intraperitoneal infection, PrPSc was detected in brain first.